PROJECT SUMMARY SLAM-family receptors are a family of cell surface receptors that play a variety of roles during the generation of innate and adaptive immune responses. Type I interferons are key cytokines that promote antiviral immunity, but if dysregulated, can contribute to the development of autoimmune diseases such as systemic lupus erythematosus. One member of the SLAM-family, SLAMF9, appears to limit the production of type I interferons in response to Toll-like receptor stimulation. Our study aims to determine how SLAMF9 functions in the immune system and its role in regulating type I interferons during viral infection or other immune stimulation. Experiments will examine the regulation of type I interferon following in vivo administration of Toll-like receptor agonists or MCMV infection. Microscopic and flow cytometric analyses will establish the cellular distribution of this receptor, with special emphasis on those cells responsible for interferon production. Lastly, the cell intrinsic mechanisms for regulating type I interferon production by SLAMF9+ cells will be studied. Key to these studies will be the functional evaluation of plasmacytoid dendritic cells and yet undefined populations of CD11b+ SLAMF9+ cells in wild type and Slamf9-/- mice. These studies will contribute to our understanding of the roles of cell surface receptors in regulating antiviral immunity and will help define cellular and molecular targets for therapeutic manipulation of type I interferons.